Osteoarthritis is a highly prevalent, progressively disabling musculoskeletal disease characterized by degeneration of articular cartilage. A significant barrier to the development of therapy for this disorder is the difficulty in assessing therapeutic interventions designed to induce the production of cartilage repair tissue. We propose the use of Fourier transform infrared (FTIR) spectroscopic analysis towards this goal. To date, our laboratory has demonstrated a significant correlation between spectra obtained from the cartilage surface using a mid-infrared fiber optic probe (mid-IFOP), and histological signs of early cartilage degradation which occur prior to macroscopic damage. We propose to build on this by extending our methodology to the setting of cartilage repair, where we envision use of the mid-IFOP as an arthroscopic diagnostic tool to evaluate repair tissue. This will be accomplished by optimization of spectral acquisition and application of chemometric methods (statistically based pattern-recognition methods used to identify or classify materials based on their spectral characteristics) to correlate spectral data with molecular characteristics of the tissue. This will provide data which is clinically useful in assessing cartilage repair while adding minimal time to arthroscopic procedures. Our methodology will first be developed in a longitudinal study of the repair process in the rabbit, and then applied to classification of repair tissue obtained by biopsy from patients. A key point in the latter analysis will be to establish the correlation between infrared spectroscopy-derived repair tissue classification and clinical outcomes. These data will lay the foundation for subsequent in vivo investigation of ongoing cartilage repair in humans. In summary, we note that there are currently no non-destructive methods available for detection and classification of subtle molecular changes in cartilage repair tissue, and for relating such changes to histologic grade and clinical outcome;therefore, the analyses we propose may represent an important advance in the emergent field of OA therapeutics. PUBLIC HEALTH RELEVANCE Articular cartilage exhibits limited capacity for self-repair, and chondral defects typically progress to widespread degradation without intervention. The development of the mid infrared fiber optic probe application could offer the ability to monitor cartilage repair tissue molecular characteristics in situ, and thus permit appropriate interventions to be undertaken on an ongoing basis. Therefore, the development of this technique may play a truly central role in the exceedingly important field of tissue regeneration by offering this capability.